Patients with renal dysfunction have been increasing worldwide and the increased number of patients with end-stage kidney disease undergoing artificial dialysis has become a medical economic problem. In recent years, the concept of disease named chronic kidney disease (CKD) has been proposed, resulting in growing the recognition for the importance of the prevention and treatment. Chronic kidney disease means the state in which “the observation of renal disease with positive proteinuria” or “reduced renal function (glomerular filtration rate less than 60 ml/min/1.73 m2)” continues over three months.
Hypertension, diabetes, dyslipidemia and smoking become risk factors for the onset and progression of chronic kidney disease and the growing number of patients in the future is feared by the spread of metabolic syndrome due to a change in life style. Chronic kidney disease is not only the risk of progression to end-stage kidney disease but also the risk factor for cardiovascular events and has become causes of myocardial infarction, heart failure, cerebral infarction and death.
For the prevention and treatment of chronic kidney disease, in addition to the life guidance and dietary advice, the treatment by antihypertensive therapy using angiotensin receptor antagonist and calcium antagonist is carried out. But more effective prophylactic and therapeutic agents for renal dysfunction are needed, because the existing therapies are not effective enough.
The pathological features in chronic kidney disease are glomerulosclerosis and tubulointerstitial fibrosis. The pathology image at end-stage renal disease is remarkable for the shedding and fibrosis of parenchymal cells. It is known that renal dysfunction progresses more rapidly in patient with than without tubulointerstitial fibrosis among patient with chronic kidney disease.
Fibrosis can occur in every tissue, while it can be progressed by common mechanisms, irrespective of the kind of trigger of its development. On the other hand, the construction of tissue and organ in animal is maintained by the fibers including collagen. When tissue receives any damage, the damaged tissue is restored to the original tissue in process of wound healing accompanied by collagen production. However, when tissue receives immunological, chemical, mechanical, metabolic or other damage several times and the degree of their damages is large, the accumulation of excess fibrous connective tissue can occur. The accumulation of such connective tissue is irreversible and the abnormal increase of fiber causes fibrotic disease in which tissues and organs are not able to function normally.
Since there is no effective agent for chronic kidney disease, particularly chronic kidney disease with fibrosis, the identification of novel enhancing factor for fibrosis that has potential for drug target is desired.